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Warren P Mason

Publications and source records attributed to Warren P Mason.

11 recordsLinked to original sources
PubMed2006

Recent advances in the treatment of oligodendrogliomas.

The optimal treatment for patients with oligodendrogliomas is unknown, and current management strategies remain controversial. This past year, further exploration of the molecular genetics of the tumors and its prognostic implications for outcome, evaluation of the utility of positron emission tomography imaging, and the role of radiation and chemotherapy in the treatment of oligodendrogliomas have been reported. It is becoming increasingly apparent that oligodendrogliomas are several distinct diseases on a molecular level, and that key genetic derangements can signify a response to treatment and favorable outcome. The added contributions of recent publications consolidates these emerging impressions. Ultimately, the combination of improved imaging techniques, molecular profiling, and new therapies should result in improved outcome with reduced treatment-related toxicity for patients with newly diagnosed, progressive, and recurrent oligodendrogliomas.

Diagnosis, Differential↗
PubMed2006

The changing management of low-grade astrocytomas and oligodendrogliomas.

Low-grade gliomas are uncommon primary brain tumors that preferentially affect young to middle-aged adults. Although they are indolent tumors, low-grade gliomas cause considerable and progressive morbidity and are ultimately fatal. Surgery and radiotherapy are the primary therapeutic options for patients with these diseases. Chemotherapy is playing a larger role in the management of patients with low-grade gliomas. Patients with oligodendrogliomas or other low-grade gliomas that harbor a distinct genetic derangement characterized by allelic loss of chromosomes 1p and 19q appear to have a superior prognosis that is due in part to a more predictable and durable response to treatment. For this subset of patients with low-grade gliomas, treatment with initial chemotherapy and deferred radiotherapy is an increasingly attractive therapeutic approach.

Astrocytoma↗
PubMed2006

Changing paradigms--an update on the multidisciplinary management of malignant glioma.

Treatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated activity against recurrent malignant glioma and efficacy if given concurrently with radiotherapy in the upfront setting. Oligodendroglioma with 1p/19q deletions has been recognized as a distinct pathologic entity with particular sensitivity to radiotherapy and chemotherapy. Randomized trials have shown that early neoadjuvant or adjuvant administration of procarbazine, lomustine, and vincristine chemotherapy prolongs disease-free survival; however, it has no impact on overall survival. Temozolomide, a novel alkylating agent, has shown modest activity against recurrent glioma. In combination with radiotherapy in newly diagnosed patients with glioblastoma, temozolomide significantly prolongs survival. Molecular studies have demonstrated that the benefit is mainly observed in patients whose tumors have a methylated methylguanine methyltransferase gene promoter and are thus unable to repair some of the chemotherapy-induced DNA damage. For lower-grade glioma, the use of chemotherapy remains limited to recurrent disease, and first-line administration is the subject of ongoing clinical trials. Irinotecan and agents like gefitinib, erlotinib, and imatinib targeting the epidermal growth factor receptor and platelet-derived growth factor receptor have shown some promise in recurrent malignant glioma. This review summarizes recent developments, focusing on the clinical management of patients in daily neuro-oncology practice.

Adult↗
PubMed2005

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.

BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. METHODS: Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. CONCLUSIONS: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

Adrenal Cortex Hormones↗
PubMed2005

Oligodendroglioma.

Surgery, radiotherapy, and chemotherapy are the standard treatment modalities for all primary brain tumors. Oligodendroglial tumors are uncommon primary brain tumors that typically are classified as low-grade or anaplastic based on their histologic appearance. A great deal of controversy has surrounded the diagnosis of an oligodendroglioma because no unique immunohistochemical marker exists to diagnose this tumor, forcing pathologists to render a diagnosis based on subjective microscopic features. Although once considered relatively rare, oligodendroglial tumors have been increasing in incidence because pathologists have become less rigorous about this diagnosis. However, recent advances in our understanding of the molecular genetic changes associated with brain tumors have identified loss of heterozygosity of chromosomes 1p and 19q as a unique genetic signature of most oligodendroglial tumors, an advance that has paved the way for pathologists to use molecular diagnostics to identify these tumors with improved reliability. These genetic derangements have significant clinical and therapeutic implications because they have been associated with a predictable and durable response to treatment, particularly chemotherapy, and an improved prognosis. The unique chemosensitivity of oligodendroglial tumors has been recognized by neurooncologists for at least 15 years, and various chemotherapeutic agents have been used to manage these diseases. However, the appropriate timing of chemotherapy, and the drugs of choice remain controversial. Increasingly, neurooncologists are reluctant to use radiotherapy as initial management for these diseases because of concerns surrounding the late neurocognitive sequelae of cranial irradiation. These toxicities are particularly important for patients with low-grade oligodendrogliomas in whom the prognosis often exceeds 10 years. Consequently, with the accumulating evidence supporting the chemosensitivity of low-grade and anaplastic oligodendrogliomas and the recent ability to use molecular diagnostics to identify a chemosensitive subset of oligodendrogliomas, neurooncologists are increasingly administering chemotherapy as the initial intervention for all oligodendroglial tumors that harbor favorable genetic derangements. Additionally, although immediate postoperative treatment is uniformly administered to patients with anaplastic oligodendrogliomas, there has been an increasing tendency to defer definitive therapy for those with low-grade oligodendrogliomas until evidence of progression. The development of temozolomide, an oral and well-tolerated alkylating agent that has activity against oligodendroglial tumors, has accelerated this trend to the extent that currently many patients with newly diagnosed low-grade and anaplastic oligodendrogliomas are offered this drug as initial treatment. This paper reviews the current management of oligodendrogliomas, with an emphasis on the expanding role of chemotherapy for these neoplasms.

Journal Article↗
PubMed2005

Progress in clinical neurosciences: Advances in the management of low-grade gliomas.

The management of low-grade gliomas represents one of the most challenging and controversial areas in neuro-oncology. Many aspects of the treatment of low-grade gliomas are debated, including the optimal timing of surgery and radiotherapy, the benefit of extensive surgery, and the impact of these variables on the natural history of these indolent and generally incurable tumours. The recently published results of several large multicentre trials addressing the timing and dose of radiotherapy have provided solid evidence for delayed and reduced dose irradiation. These studies have also confirmed prognostic variables that can be used to guide management of individual patients. Among these variables is the observation that tumours with oligodendroglial features have a better natural history and response profile. The recognition that as many as two thirds of low-grade gliomas have oligodendroglial features, advances in molecular diagnostics making accurate pathologic diagnosis of oligodendroglial tumours possible, and the established chemosensitivity of malignant oligodendrogliomas, have raised new issues surrounding the potential value of chemotherapy for low-grade gliomas. This review will be restricted to low-grade diffuse astrocytomas, oligodendrogliomas, and low-grade mixed oligoastrocytomas in adults, and provide evidence-based guidelines for the management of these tumours, including the emerging role of chemotherapy as initial treatment.

Adult↗
PubMed2005

Drug Insight: temozolomide as a treatment for malignant glioma--impact of a recent trial.

Glioblastoma multiforme is the most common primary brain tumor in adults. Until recently, the standard of care consisted of maximal surgical resection followed by external beam radiotherapy. The role of adjuvant chemotherapy for newly diagnosed glioblastoma has been controversial; most of the numerous randomized phase III trials conducted over the past 40 years have failed to show a statistically significant and clinically meaningful survival advantage for patients randomized to the chemotherapy arm. Consequently, the choices of chemotherapeutics for patients with glioblastoma have been limited, and cytotoxic treatment regimens have usually included a nitrosourea. Temozolomide, a relatively new orally administered methylating agent, has demonstrable activity in glioma. A recent trial conducted under the auspices of the European Organization for the Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has defined a role for temozolomide in the initial management of glioblastoma. A companion correlative tumor-biology study has identified epigenetic silencing of the promoter of the gene that encodes MGMT (O6-methylguanine-DNA methyltransferase) in tumor specimens as a strong and independent prognostic factor for survival among patients with a newly diagnosed glioblastoma, as well as a predictor of survival benefit from chemoradiotherapy with temozolomide. This review briefly summarizes the development of temozolomide as a therapy for patients with malignant brain tumors, emphasizing recent trials that have established a new standard of care for patients with glioblastoma and speculating on how these advances might influence future therapeutic investigations for malignant primary brain tumors.

Antineoplastic Agents, Alkylating↗
PubMed2003

Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.

PURPOSE: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue. RESULTS: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity. CONCLUSION: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.

Adult↗
PubMed2002

Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma.

OBJECT: The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas. METHODS: Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31-75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy. All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8-151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively: the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression. CONCLUSIONS: Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.

Adult↗